From 2000 to 2017 the Sabin Vaccine Institute partnered with the Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine in Houston, Texas to develop safe, effective and low-cost vaccines for infectious and neglected tropical diseases. Baylor College of Medicine and Texas Children’s Hospital Center for Vaccine Development continue this research as of May 2017.

Organism: Trypanosoma cruzi

Vaccine Candidate: Tc24 and TSA-1

Stage of Development: Pre-clinical

Years Sabin conducted research: 2011-2017

Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease largely found in the Americas that affects over 6.7 million people and can lead to severe cardiac and intestinal complications.

About the Vaccine

The Sabin Vaccine Institute Product Development Partnership (Sabin PDP) advanced research of two candidate antigens to develop a low-cost, safe and effective vaccine for Chagas disease. Working together with a network of global partners, Sabin PDP led research on two Trypanosoma cruzi candidate antigens, Tc24 and TSA-1. The Sabin PDP launched the Chagas disease vaccine program in 2011, and this research could ultimately lead to the first therapeutic vaccine for Chagas disease. As of May 2017, Baylor College of Medicine and the Texas Children’s Hospital’s Center for Vaccine Development continue this research.

The project partners have successfully developed a reproducible process for scalable production, formulation and testing of recombinant Tc24-C4, a parasite candidate antigen. The protein was formulated with an adjuvant and evaluated both as a stand-alone technology and in a vaccine-linked chemotherapy approach with benznidazole, the current treatment for Chagas disease. Early studies in mouse models show a potent immune response, increased host survival, diminished cardiac fibrosis and pathology, and reduced cardiac parasite loads.

About Chagas Disease

Chagas disease is most commonly a vector borne disease, caused by the T. cruzi parasite transmitted through a bite from an infected triatomine bug – commonly called the “kissing bug” because of its tendency to bite near the mouth. Chagas disease disproportionately affects the poorest populations in the Americas, as the kissing bug often lives in poor-quality dwellings and in areas where vector control practices are weak.

Following initial exposure to the T. cruzi parasite, individuals develop acute infection, which lasts for four to eight weeks. More than thirty percent of infected people later develop cardiac and gastrointestinal symptoms, which can lead to disability and even death. Most of the disability and deaths from Chagas disease result from chronic Chagas cardiomyopathy, characterized by arrhythmias, aneurysms and heart failure. Most infected individuals do not know they have Chagas disease.

Chagas disease has also emerged as an important global maternal-child health problem. An estimated 11 percent of pregnant women in Latin America are infected with T. cruzi at any given time, and between 5-10 percent of those pregnant women pass the infection to their unborn fetus.

While most sufferers from Chagas disease reside in impoverished areas of Latin America and in Texas in the United States, there has been a trend towards the recent globalization of Chagas disease over the last two to three decades resulting in a significant disease burden in Europe, as well as several thousand cases now in Japan. On top of the severe health effects outlined above, Chagas disease healthcare and other costs are estimated to exceed $7 billion annually.

Why We Need a Vaccine

Current treatment is dependent on two drugs, benznidazole or nifurtimox, both of which are highly effective when therapy is initiated at the onset of infection and during the acute phase of the disease. However, very few patients are diagnosed in the acute stages because many people are asymptomatic when first infected, or because the patients do not have access to proper diagnosis and treatment.

The efficacy of both drugs for many patients with chronic Chagas disease diminishes the longer a person has been infected. Available drug treatments have a high level of toxicity and cause side effects severe enough to require interruption of treatment in some patients. Thus, the benefits of medication in preventing or delaying the development of Chagas disease has to be weighed against the long duration of treatment (up to two months) and relatively high rates of adverse reactions that occur in up to 40 percent of treated patients. Additionally, there is currently no available drug intervention for pregnant women infected with T. cruzi. Treatment regimens, for those who can take them, are long and costly.

A successful therapeutic vaccine would shorten the time required for treatment and save on costs associated with current treatments. Recent models demonstrate the use of a therapeutic vaccine to be highly cost-effective relative to chemotherapy and preventative vaccines.

The London Declaration on Neglected Tropical Diseases, signed in 2012, calls for the control of Chagas disease. While improved vector control practices and early drug treatment during acute infection may help control the incidence of chronic Chagas disease, there are no current methods to control congenital transmission. A therapeutic vaccine, given to pregnant women infected with T. cruzi, may reduce the risk of transmitting the infection to their unborn babies.